A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

Sofer, Tamar; Kurniansyah, Nuzulul; Granot-Hershkovitz, Einat; Goodman, Matthew O.; Tarraf, Wassim; Broce, Iris; Lipton, Richard B.; Daviglus, Martha; Lamar, Melissa; Wassertheil-Smoller, Sylvia; Cai, Jianwen; DeCarli, Charles S.; Gonzalez, Hector M.; Fornage, Myriam

doi:10.1186/s13195-023-01298-3

Alzheimer's Research & Therapy

Table 3 Estimated associations of AD PRS and of APOE allele counts with MCI

From: A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

Study	GWAS Population	#SNP	APOE-ϵ2	P	APOE-ϵ4	P	PRS	P
PRS includes APOE region SNPs, analysis unadjusted for APOE alleles
FinnGen	Finish	81	–	–	–	–	1.17[1.06;1.29]	2.00E-03
Jun et al	Multi-Ethnic	85	–	–	–	–	1.10[1.00;1.21]	0.05
Bellenguez et al	White	1937	–	–	–	–	1.07[0.97;1.18]	0.17
Kunkle et al. 2019 [17]	White	12002	–	–	–	–	1.27[1.01;1.61]	0.04
Kunkle et al. 2021 [13]	Black	157	–	–	–	–	1.11[1.01;1.22]	0.03
PRSsum	Multi-Ethnic	14100	–	–	–	–	1.19[1.07;1,32]	9.16E-04
PRS includes APOE region SNPs, analysis adjusted for APOE alleles
FinnGen	Finish	81	1.02[0.71;1.47]	0.91	0.95[0.73;1.22]	0.67	1.19[1.06;1.33]	3.00E-03
Jun et al	Multi-Ethnic	85	0.95[0.66;1.36]	0.78	0.89[0.65;1.21]	0.46	1.15[1.01;1.31]	0.04
Bellenguez et al	White	1937	0.98[0.68;1.40]	0.89	1.09[0.85;1.38]	0.5	1.06[0.96;1.18]	0.27
Kunkle et al. 2019 [17]	White	12002	0.98[0.68;1.41]	0.91	1.06[0.84;1.35]	0.61	1.34[1.05;1.71]	0.02
Kunkle et al. 2021 [13]	Black	157	0.95[0.66;1.36]	0.77	0.96[0.74;1.25]	0.75	1.14[1.02;1.28]	0.02
PRSsum	Multi-Ethnic	14100	1.02[0.71;1.46]	0.92	0.81[0.61;1.09]	0.16	1.28[1.12;1.46]	2.00E-04
PRS excludes APOE region SNPs, analysis adjusted for APOE alleles
FinnGen	Finish	34	0.96[0.67;1.38]	0.83	1.08[0.85;1.38]	0.51	1.14[1.03;1.27]	0.02
Jun et al	Multi-Ethnic	38	0.95[0.67;1.36]	0.79	1.10[0.86;1.39]	0.45	1.04[0.94;1.15]	0.48
Bellenguez et al	White	1871	0.96[0.67;1.37]	0.8	1.10[0.86;1.39]	0.45	1.03[0.93;1.14]	0.62
Kunkle et al. 2019 [17]	White	11805	0.96[0.67;1.37]	0.81	1.10[0.86;1.39]	0.45	1.27[0.99;1.63]	0.06
Kunkle et al. 2021 [13]	Black	146	0.95[0.67;1.36]	0.79	1.10[0.86;1.39]	0.45	1.11[1.00;1.22]	0.05
PRSsum	Multi-Ethnic	13807	0.96[0.67;1.38]	0.82	1.09[0.86;1.39]	0.46	1.17[1.04;1.31]	0.01

For each PRS, we estimated its association as well as the APOE-\(\epsilon 4\) and APOE-\(\epsilon 2\) allele counts associations with MCI in a joint model accounting for these variables together, and further adjusting for age at HCHS/SOL baseline visit, time between the baseline and SOL-INCA visit, sex, study center, and 5 first principal components of the genetic data. In the top part of the table the PRSs includes APOE-region SNPs and the analysis is not adjusted for APOE allele counts. In the middle part, the PRS associations are adjusted for APOE allele counts. At the bottom, APOE-region SNPs were excluded from the PRSs in analyses that do not adjust for APOE alleles

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ISSN: 1758-9193

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